| Abstrakt: |
Zika virus (ZIKV), a neglected tropical disease until its re-emergence in 2007, causes microcephaly in infants and Guillain-Barré syndrome in adults. Its re-emergence and spread to more than 80 countries led the World Health Organization in 2016 to declare a Public Health Emergency. ZIKV is mainly transmitted by mosquitos, but can persist in infected human male semen for prolonged periods and may be sexually transmitted. Testicular Sertoli cells support ZIKV replication and may be a reservoir for persistent ZIKV infection. Electrical impedance analyses indicated ZIKV infection rapidly disrupted Vero cell monolayers but had little effect upon human Sertoli cells (HSerC). We determined ZIKV-induced proteomic changes in HSerC using an aptamer-based multiplexed technique (SOMAscan) targeting >1300 human proteins. ZIKV infection caused differential expression of 299 proteins during three different time points, including 5 days after infection. Dysregulated proteins are involved in different bio-functions, including cell death and survival, cell cycle, maintenance of cellular function, cell signaling, cellular assembly, morphology, movement, molecular transport, and immune response. Many signaling pathways important for maintenance of HSerC function and spermatogenesis were highly dysregulated. These included IL-6, IGF1, EGF, NF-κB, PPAR, ERK/MAPK, and growth hormone signaling. Down-regulation of the PPAR signaling pathway might impact cellular energy supplies. Upstream molecule analysis also indicated microRNAs involved in germ cell development were downregulated by infection. Overall, this study leads to a better understanding of Sertoli cellular mechanisms used by ZIKV during persistent infection and possible ZIKV impacts on spermatogenesis. Author summary: Zika virus has gained new significance during the past few years when it became associated with increased numbers of birth defects. Zika virus is primarily transmitted by mosquitoes. However, it is becoming increasingly clear that there are other ways the virus can be transmitted. One of these ways is through sexual transmission. In order to better understand how Zika virus can persist in humans and may be transmitted sexually, we examined the interactions between Zika virus and Sertoli cells, a specialized male testicular cell responsible for sperm production. We examined how Zika virus infection affected more than 1300 Sertoli cell proteins and found that virus infection altered cellular pathways responsible for sperm production. At the same time, Zika virus had little effect upon overall structure of the cells. This information helps better explain the long-lived persistence of Zika virus in human male reproductive cells and the virus' capacity to be sexually transmitted. [ABSTRACT FROM AUTHOR] |
